Our current knowledge of aspects of bacterial life, be it metabolic activities or pathogenesis, is mostly obtained by studying bacteria in monospecies cultures. Nevertheless, in nature bacteria almost always exist in multispecies communities. How the presence of other species affects the metabolic activity or the pathogenic capacity of a particular bacterium is an important question not only to basic research microbiologists, but also to clinical microbiologists. It has been well established that the indigenous microflora on the human body play an important role in the health and disease of the human host. For example, some of the most prevalent infectious diseases such as Dental caries, periodontal diseases, vaginitis, and inflammatory bowel syndrome are believed to be caused by a shift of the indigenous microflora composition. Therefore, understanding how different species interact in a multispecies community could help devise appropriate control measures to curb these polymicrobial diseases. In this grant, we propose to use the Dental caries pathogen, Streptococcus mutans, as a model organism and the Dental plaque as a model system to understand inter-species interactions in a multispecies microbial community. Two Specific Aims are proposed: Aim 1. Using microarray to hunt for the genes of S. mutans responding to interspecies interactions. Aim 2. Using a random mutagenesis approach to identify and characterize genes regulating the response of S. mutans to other species. A variety of state-of-the-art analytical tools will be used to achieve these Aims. [unreadable] [unreadable] [unreadable]